Myristyl-gamma-picolinium chloride suppresses cartilage and synovial membrane glycosaminoglycan synthesis.

Myristyl-gamma-picolinium chloride (MGP) is a novel constituent of methylprednisolone acetate suspensions used for intra-articular corticosteroid therapy. Hyaluronic acid synthesis in organ cultures of normal canine synovial villi incubated with MGP was reduced in proportion to MGP concentration. Similar dose-dependent inhibition of sodium sulfate S 35-labeled glycosaminoglycan synthesis was observed in organ cultures of canine articular cartilage treated with MGP. In comparison, the intact cartilage of cultured femoral condyles appeared less sensitive to MGP inhibition of glycosaminoglycan synthesis. Cartilage and synovium were examined 4 hours after an intra-articular injection of either MGP or its vehicle into canine stifles. No differences in Na2(35)SO4-glycosaminoglycan synthesis were observed between cartilage organ cultures prepared from the MGP-treated and the contralateral vehicle-treated joints, but in four of the five dogs studied less hyaluronic acid was synthesized (P less than 0.05) by synovial cultures from joints exposed to MGP than by cultures from the contralateral joints. Synovium from the MGP-treated joints remained capable of phagocytosis. These observations indicate that at clinically relevant concentrations MGP can inhibit synovial hyaluronic acid synthesis, but has little metabolic effect on normal articular cartilage.